Diarrhea is a common complaint in DM. Diarrhea is defined as having more than three bowel movements per day, urgency, or loose, watery stools. According to one study, the adjusted odds ratio for diarrhea was 2.06 in patients with diabetes when compared with controls, with a prevalence of diarrhea at 15.6 % [14].

Etiologies of diarrhea in diabetes are multifactorial and include rapid intestinal transit, drug-induced diarrhea, small intestine bacterial overgrowth, celiac disease, pancreatic exocrine insufficiency, dietary factors, anorectal dysfunction, fecal incontinence, and microscopic colitis [1]. Some of these etiologies are discussed separately later in this chapter.

A single or combination of multiple pathophysiological mechanisms may be responsible for diabetic diarrhea. Some of these mechanisms include diabetic enteropathy, decreased α2- adrenergic input, and intestinal dysmotility resulting in shortened or prolonged transit time. Medications (e.g., acarbose and miglitol) and dietary products (e.g., artificial sweeteners) can cause osmotic diarrhea. Metformin, which originates from a plant called goat’s rue (Galega officinalis), increases the risk of diarrhea by threefold. This is related to decreased disaccharidase activity at brush border and increased serotonin levels [15]. Diarrhea can be early or late onset and is typically associated with dose escalation. Orlistat can cause fat malabsorption. Celiac disease and microscopic colitis are other common causes. Autoimmune pancreatitis can be associated with T1DM, resulting in pancreatic exocrine insufficiency and diarrhea [1, 16]. Diarrhea can be present when diabetes is a result of chronic pancreatitis (pancreatic diabetes [type 3C diabetes]). Autonomic neuropathy from poor glycemic control can affect anal sphincter function and rectal sensation, leading to fecal incontinence and diarrhea [1]. Autonomic neuropathy can also lead to orocecal transit time of <30 min, resulting in rapid intestinal transit and diarrhea [17]. It is important to differentiate whether diarrhea is caused by rapid intestinal transit vs. SIBO. Nuclear scintigraphy in combination with hydrogen breath tests can be helpful in this situation [17]. Newer technology such as wireless motility capsule may also be utilized [18]. This differentiation has key clinical implications with regard to the use of antimotility agents or antibiotics in a particular case. Figure 4.2 shows a diagnostic algorithm to help navigate a case of diabetic diarrhea [1].

Treatment of diabetic diarrhea starts with improved glycemic control. According to one study, patients with self-reported good glycemic control had a prevalence of 12.3 % of diarrhea symptoms, while those with poor control had a prevalence of 32.4 %. [14]. Identification of a specific etiology for diabetic diarrhea provides an opportunity for focused, effective therapy. Eliminating potential medicine or dietary triggers is important. Those with well-documented SIBO respond well to a rotating antibiotic regimen. Nonspecific therapy with loperamide generally controls rapid intestinal transit. More potent opiates (e.g., deodorized tincture of opium) are occasionally required. In patients who do not respond, clonidine, a α2-adrenergic agonist, can also treat idiopathic diarrhea [3]. However, it should be used with caution, given the potential for hypotension. Octreotide is another option in the diabetic patient with difficult-to-control diarrhea [19].

SIBO is characterized by alterations in the type and quantity of bacteria within the small intestine, resulting in significant changes in the microbiota of the small intestine causing gastrointestinal symptoms. In the general population, prevalence of symptomatic SIBO is estimated to be closer to 6 % [20]. However, the incidence of SIBO in patients with DM and diarrhea is much higher, approaching closer to 50 % in one study [20].

The pathology of SIBO is related to decreased acid in the stomach (acid decreases overall bacterial burden), abnormal gastrointestinal motility and slow transit (leads to stasis of intestinal contents and subsequent bacterial overgrowth), or structural abnormalities from surgeries, particularly blind loops, may also create reservoirs that enable overgrowth of bacteria. DM is known to cause gastroparesis and abnormal intestinal motility.

SIBO leads to carbohydrate malabsorption (due to disruption of intestinal brush border resulting in decreased disaccharidase activity), excessive gas production (from carbohydrate digestion by bacteria), and generation of inflammatory cytokines, short-chain fatty acids, and bile salt deconjugation. Due to bacterial deconjugation of bile salts, SIBO may lead to fat malabsorption and steatorrhea and subsequent deficiency of Vitamin A, D, E, and K [21]. Bile salt deconjugation may also lead to bile acid diarrhea due to direct secretory effect of bile acids on colonic mucosa and impaired enterohepatic reabsorption [22]. Anaerobic bacteria scavenge vitamin B12 leading to its deficiency. Figure 4.3 delineates the factors affecting development of SIBO [22, 23].

The typical symptoms of SIBO are nonspecific and include abdominal pain with bloating, gas, and diarrhea. Other frequently reported symptoms include flatulence, abdominal distension, and weakness. The symptoms are frequently vague and overlap with IBS-D. In patients with DM and the above symptoms, SIBO should be considered.

Quantification of bacteria from jejunal aspirate on EGD is the gold standard for diagnosis. A cutoff value of 100,000 CFU/mL is used. The test is costly, and it is cumbersome to handle specimen and difficult to culture intestinal bacteria, which makes it less practical. Other noninvasive tests such as glucose hydrogen breath test lack sensitivity, specificity, and accuracy when compared to bacterial quantification [24]. However, glucose hydrogen breath test when performed in combination with measurement of intestinal transit increases the accuracy of diagnosis. Given its practicality, empiric treatment with antibiotics is an acceptable alternative in most cases with suspected SIBO.

Management includes correction of the underlying conditions (such as impaired motility and poor glycemic control), correction of nutritional deficiencies (fat-soluble vitamins and vitamin B12), and use of antibiotics. Specifically for DM where intestinal motility may be impaired, good glycemic control and short-term use of prokinetics are advised. The most well studied and extensively used antibiotic is rifaximin for SIBO; however, its cost is a deterrent for routine use. Recurrence of SIBO is common and may respond to repeated courses of antibiotics. In refractory cases, patients may require continuous cycling of antibiotics to control symptoms. Judicious use of antibiotics is recommended. Table 4.1 delineates the antibiotic type and its duration for treatment of SIBO [25].

Fecal incontinence may affect up to 9 % of non-institutionalized US adults and is more common with older age [26, 27]. Specifically with diabetes, the odds ratio of developing fecal incontinence is 1.5 according to the largest cross-sectional study to date based on the National Health and Nutrition Examination Survey (NHANES) database [26, 27]. Incontinence can be primary, caused by anorectal dysfunction, or secondary as a result of diarrhea. Fecal incontinence is related to autonomic neuropathy, impaired rectoanal reflex, and direct effect of glycemic control on internal anal sphincter [28, 29]. In a study evaluating anorectal sensory and motor function, researchers found that diabetic patients with fecal incontinence required a significantly larger volume to experience rectal sensation, which in turn leads to overflow incontinence [29]. Alternate etiologies such as damage to the internal anal sphincter from previous childbirth, surgery, or trauma should also be excluded. Fecal incontinence is distinct from stool seepage, producing soilage of undergarments that may result from hemorrhoids, enlarged skin tags, poor hygiene, fistula-in-ano, and rectal mucosal prolapse. Fecal incontinence manifests with low volume “diarrhea,” and nocturnal symptoms are common.